Taming PH3: State of the Art and Future Directions in Synthesis

Appetite for reactions involving PH3 has grown in the past few years. This in part is due to the ability to generate PH3 cleanly and safely via digestion of cheap metal phosphides with acids, thus avoiding pressurized cylinders and specialized equipment. In this perspective we highlight current trends in forming new P–C/P–OC bonds with PH3 and discuss the challenges involved with selectivity and product separation encumbering these reactions. We highlight the reactivity of PH3 with main group reagents, building on the early pioneering work with transition metal complexes and PH3. Additionally, we highlight the recent renewal of interest in alkali metal sources of H2P– which are proving to be useful synthons for chemistry across the periodic table. Such MPH2 sources are being used to generate the desired products in a more controlled fashion and are allowing access to unexplored phosphorus-containing species.


INTRODUCTION
There is an acute need to undertake drastic changes in the way we consume the Earth's vital and finite resources, with much of this linked to changes needed to policies and practices of governments. 1,2 However, this should also bring into strong focus our need to undertake sustainable synthesis. 3,4 With this comes the need to develop new methods with which to undertake novel bond transformations; use reagents that avoid the generation of exogenous waste which requires protracted purification procedures; move away from harmful solvents; use feedstocks that are less activated (or come directly from the source, e.g., in the Earth's crust); and use metals that are abundant (e.g., rock-forming metals) both in heterogeneous/ homogeneous catalysis and in devices/materials. 5 Rather than providing prescriptive coverage of all reports on transformations involving PH 3 , including the pioneering research into stoichiometric reactions with PH 3 , 6 this perspective serves to highlight trends in the applications of PH 3 , the "routine" P−C bond forming reactions that are basemediated (i.e., reductive coupling) or involve the hydrofunctionalization of unsaturated bonds. This perspective will also cover more unusual transformations that form P−C bonds via other means, along with modern main group bond transformations and reactions with metals (Scheme 1).
The latter portion of this perspective goes beyond PH 3 and showcases the chemistry of the H 2 P − anion. Recently, the use of alkali metal phosphides as a source of H 2 P − has been receiving renewed interest. We will highlight some of the remarkable implementations of such salts, both in organic transformations and as promising reagents in the preparation of notable main group, transition metal, and f-block metal species.
We would be remiss not to briefly mention the numerous reports, during a prolific period of PH 3 research that took place between the late 1960s through to the early 1990s, on the reaction between PH 3 and transition metal (TM) com-plexes. 7−15 Formation of TM complexes bearing the [TM]− PH 3 motif as well as formal oxidative addition/hydride abstraction to form [TM]−PH 2 and [TM]−(μ-PH 2 ) motifs have been identified, with analysis ranging from multinuclear NMR and IR data only, through to those also reporting single crystal X-ray diffraction data. For example, Jones and coworkers reported the formation and isolation of a remarkably air-stable trans-[RuCl 2 (PH 3 ) 4 ] complex. 16 However, further study into reactivity with these complexes has rarely been explored 17 and will therefore not be the focus of this perspective. However, this highlights the many seemingly simple areas of PH 3 research that are yet to be fully investigated.

AN IMPORTANT NOTE ON SAFETY
It would be irresponsible not to emphasize the dangers associated with handling PH 3 . PH 3 is a highly toxic gas that is spontaneously flammable in air. The American Conference of Governmental Industrial Hygienists (ACGIH) places a timeweighted average limit on exposure at 0.05 ppm (which is the concentration of a substance to which most workers can be exposed without adverse effects), with a short-term exposure limit of 0.15 ppm (which means a 15 min time-weighted average exposure should not be exceeded at any time during an 8 h workday). 18 The National Institute for Occupational Safety and Health (NIOSH) list 0.3 ppm as the time-weighted average limit and 1 ppm as the short-term exposure limit (10 h, 15 min respectively). The US Environmental Protection Agency lists that the 4 h LC 50 for PH 3 in rats is 11 ppm. 19 To put these numbers into context, the NIOSH time-weighted average limit for CO is 35 ppm and the NIOSH short-term exposure limit for HCN is 4.7 ppm, 20 while the 1 h LC 50 for HCN in rats is 139−144 ppm. 21,22 In short, handling of pressurized cylinders of PH 3 requires a robust risk assessment/ COSHH assessment and rigorous safety protocols, not least a PH 3 monitor to ensure the safety of not only the chemist handling the substance but also other researchers in the lab. The fume hood setup must include NaOCl scrubbers or a PH 3 burner/H 2 O spray to quench unreacted PH 3 . Akin to our responsibility to study and develop more sustainable approaches to synthesis, safe use and quenching of this toxic gas, avoiding exposure of researchers and the environment to this species, is paramount.

REACTING PH 3 TO FORM P−C/P−OC BONDS
PH 3 is the next downstream output from elemental phosphorus, which comes directly from industrial large-scale processing of phosphate rock. 23 Numerous reviews on functionalization of P 4 exist, but the tetra-nuclear nature of this feedstock means that controlled, direct, or catalytic functionalization of P 4 into, for example, 4PR 3 is not welldocumented. 24,25 Instead, conversion of P 4 into PH 3 or PCl 3 and onward reaction to form organophosphines is the more traditional pathway. Onward reactions of PCl 3 with organic substrates to prepare P−C(sp 3 ) bonds are well documented, but wasteful in terms of atom economy. P−C bond forming reactions with PH 3 range from stoichiometric-in-base-mediated reactions with alkyl halides through to hydrophosphination in the presence of a metal catalyst, radical initiator, or a base. In many cases we invariably access products of the form PR 3 , although there are examples where HPR 2 and H 2 PR are produced (vide infra). Even the hydrophosphination literature has limitations: work on catalytic hydrophosphination has routinely reported on the formation of the tertiary phosphine product as the major species, and only limited progress in diversifying the structure of the products, or the reaction selectivity, has been made. The reason that PR 3 is formed preferentially can be linked to the enhanced reactivity of the product compared to the starting materials, i.e. PH 3 < H 2 PR < HPR 2 , and accessing H 2 PR or HPR 2 tends to be achieved by limiting substrate stoichiometry rather than any greater form of reaction control. Stoichiometric-in-base transformations are simple to undertake and are well documented, but it could be argued that they serve to demonstrate the limitations in the organic transformations undertaken using PH 3 : the reaction of RCl + base + PH 3 is simply the inverse of the classical method of using RH + base (or RCl + 2base) + PCl 3 . PH 3 is a reactive substrate, and the early work on the formation of phosphonium salts from PH 3 and formaldehyde dates back to at least 1888, 26 with applications from this seminal study still very relevant today. 27 Building upon work from Stiles et al. using photochemical initiation, 28 an early report on catalytic functionalization of PH 3 came from Rauhut and co-workers 29 where they disclosed the hydrophosphination of acrylonitrile using PH 3 and aqueous KOH at room temperature. The reaction is mild, but is somewhat lacking in control, producing mixtures of primary, secondary, and tertiary cyanoethyl phosphines. Excess acrylonitrile allowed the formation of the tris-substituted product in 80% yield, and the secondary product could be formed in 58−63% when an excess of PH 3 is employed, while the primary cyanoethyl species is formed in 52% yield, but an autoclave operating at high pressure of PH 3 is needed (28−32 atm). The mono-and bis-substituted products were further employed in radicalmediated hydrophosphination reactions. 30 Rauhut and coworkers also employed azobis(isobutyronitrile) (AIBN) as a radical initiator to hydrophosphinate with a range of alkenes in the presence of PH 3 . 30 Interestingly, although the ratio of primary/secondary/tertiary organophosphine product is often in the region of 1:1:1, reactions with unactivated systems such as 1-octene, 1-dodecene, cyclohexene, isobutylene, and butyl vinyl ether are reported (Scheme 2). In fact, 1-octene (1 mol), PH 3 (0.33 mol), and AIBN (5 mol %) is an exothermic reaction that generated a reaction temperature of 80−100°C and produced 83% tris(octyl)phosphine cleanly after 6 h; this reaction is furthermore impressive as transformation of unactivated reagents has largely eluded modern hydrophosphination catalysis. 31 Similar to the earlier work of Rauhut and co-workers, Trofimov and co-workers have recently reported basemediated hydrophosphination of 2 equiv. of styrene (or 4-tBu-styrene) with PH 3 . The authors have published two possible onward transformations. The first is oxidation, to generate the anti-Markovnikov secondary phosphine oxide product, which is then used as a nucleophile to react with an aldehyde and finally, in the presence of FeCl 3 , hydroxide abstraction to generate a carbocation in an S N 1-type process. This then allows cyclization to form a phosphinoline oxide product (Scheme 3a). 32 The second possible onward transformation is P−O or P−N bond formation at the para-position of azobenzenes, using a simple base to carry out the coupling reaction (Scheme 3b). 33 The UV/vis-mediated isomerization of the azo functionality was then investigated. Ragogna employed AIBN to prepare tertiary fluorinated alkyl phosphines which can then be transformed into phosphonium salts to attenuate the properties of UV-curable resins. 34 Ragogna has also employed the early methods to prepare phosphinated lignin, which is effective as a metal scavenger. 35 A hydrophosphination that, unsurprisingly, does not need any activating agents or a catalyst is the reaction of PH 3 with the highly activated imine 1,1,1,3,3,3-hexafluoropropan-2imine, generating 4.75 g (96% yield) of the geminal substituted NH 2 ,PH 2 product from a large-scale synthesis. 36 In contrast, many hydrophosphination reactions involving PH 3 have employed transition metal catalysts; Pringle undertook the seminal work in this field and used platinum chloride salts, as well as tetrakis(phosphino) Pt, Pd, and Ni complexes for the reaction of formaldehyde with PH 3 . 37−39 Pringle also reported the use of [Pt(norbornene) 3 ] as an effective precatalyst for the reaction of PH 3 with ethyl acrylate. 40 Finally, a series of tris(phosphino) Ni, Pd, Pt catalysts as well as tris(phosphino) iridium chloride complexes were reported as competent catalysts for the hydrophosphination of acrylonitrile. 41,42 For all three unsaturated substrates the tertiary PR 3 product is formed as the sole product, although a mixture of products is often observed in situ due to the stepwise nature of the reactions. A generic catalytic cycle involves coordination of PH 3 with the unsaturated M(0) center, oxidative addition (OA) to generate a mixed metal(II) hydrido phosphide species, and then insertion of the unsaturated bond into the M−H bond followed by a reductive 1,2-shift step to generate the M−PR 3 product. An alternative pathway for formaldehyde involves a nucleophilic attack on the carbonyl moiety by M−PH 2 forming a zwitterion, and then hydride transfer generates the M−PR 3 product (Scheme 4).
More recently Trifonov reported the use of 1,3-diisopropylimidazol-2-ylidene and 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene as well as their complexes [(Me 3 Si) 2 N] 2 M(NHC) 2 ] (M = Ca, Yb, Sm) as precatalysts for hydrophosphination with PH 3 . Remarkably, they report the generation of primary phosphines based on the feedstock stoichiometry. 43 A particularly intriguing reaction from this publication is the formation of tri(Z-styryl)phosphane; the acidic nature of both the phenylacetylene and PH 3 along with the selectivity for the kinetic all-Z product is remarkable. Transformations of this type warrant further investigation in terms of substrate scope (and with this E/Z selectivity) and onward functionalization with an eye toward applications.
Stoichiometric transformations are prevalent in the literature and follow similar trends in terms of the products formed and the makeup of the transformation. For example, Stelzer and Sheldrick report a KOtBu route to prepare water-soluble phosphindoles/phosphindole oxides from PH 3 . 44 Stelzer has also reported on exploiting the inherent equilibrium between PH 3 + OH − ⇌ H 2 P − + H 2 O when aqueous DMSO/KOH solution (or with the inclusion of phase transfer catalysts such as (nBu) 4 NCl) is used, thus allowing generation of low concentrations of the highly nucleophilic H 2 P − ion for the selective reaction with organohalides forming (stoichiometrydriven) primary or secondary alkyl phosphines, bis(alkyl)phosphines, and cyclic phosphines (Scheme 5a). 45 Stelzer and co-workers have also employed iodine to prepare structurally exciting PH 2 −BINAP (1,1′-binaphthyl) and PH−BINAP systems (Scheme 5b). 46 Borangazieva and co-workers have reported an I 2 /pyridine system for the formation of trialkyl phosphates from PH 3 and methanol/ethanol/butanol/amyl alcohol/octanol. 47 This methodology was further extended to the preparation of primary aminoalkyl phosphines. 48 A change to stoichiometric CuCl 2 in CCl 4 gives selective formation of the dialkyl phosphite (HP(O)(OiPr) 2 ) when isopropanol is employed (Scheme 6). 49 Further study into the reaction, and inclusion of quinone as a reductant, has also been reported. 50 However, in general, secondary and primary species are observed as side products in many reactions. Given the challenges associated with purification of reactive phosphines, particularly those that are the product of hydrophosphination reactions (where the product is invariably an alkyl phosphine and thus more prone to oxidation), selective synthesis of a primary or secondary or tertiary phosphine is desirable. Moreover, when we look at commercial organophosphines, very few tertiary monophosphines are symmetrically substituted; there are key organophosphines such as PPh 3 , PCy 3 , and PtBu 3 , but organophosphines routinely used in, for example, cross-coupling reactions include SPhos (2dicyclohexylphosphino-2′,6′-dimethoxybiphenyl) and XPhos (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl), and bis(phosphines) such as dppf (1,1′-ferrocenediyl-bis(diphenylphosphine), XantPhos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene), and dppe (1,2-bis(diphenylphosphino)ethane) to name but a few. Here we raise another issue of a pure atomeconomy-driven approach to PH 3 functionalization: that being that the preparation of P−Ar bonds is limited to work from Dorfman and Levina, and more recently Wolf (vide infra).

PH 3 REACTING WITH COMPOUNDS OF THE p-BLOCK
In the 1990s, Cowley and Jones undertook investigations into the reactivity of PH 3 with an alkyl gallium compound with a view to preparing precursors for OMCVD processes (organometallic chemical vapor deposition). The authors present a highly sensitive μ-PH 2 cluster which undergoes slow decomposition at 200°C (Scheme 7). 51 Further reports on reactions of PH 3 , which we may consider being in the realm of main group bond transformations, are those involving NHCs and their heavier group 14 congeners. Gruẗzmacher and Pringle reported the in situ generation of the SIPr (1,3-bis(2,6-diisopropylphenyl)imidazolidine-2-ylidene) NHC (1, Scheme 8) from the chloride salt, which forms the PH 2 -imidazolidine product (2) from reaction with PH 3 and base (or the tert-butoxide adduct of NaPH 2 ). This product can then undergo hydrogen abstraction, driven by the aromatization of ortho-quinone, which allows the formation of the formal phosphinidine-carbene adduct (3). 52 This latter species was shown to undergo complexation with HgCl 2 .
Ragogna and Power have shown that PH 3 can oxidatively add to tetrylenes. The authors note a divergence in reactivity when comparing the chemistry of NH 3 53−56 and PH 3 ; the former gives the OA product with Ge and the arene elimination dimeric product with the Sn congener (Scheme 9). However, when PH 3 is employed a mixture of the OA and arene elimination dimer is formed with both Ge and Sn (the OA product is the major species in both cases). 57 Similar to the work of Ragogna and Power, where there is a discrepancy between the reactivity of the lighter and heavier pnictogens, Driess has demonstrated a difference in reactivity of PH 3 compared to AsH 3 when undertaking OA to silylene compounds. 58 PH 3 generates the OA product, whereas with AsH 3 , although OA takes place, there is an equilibrium between the arsenide product and the isomerized arsinidine species, making use of the ligand system to invoke this process. Mitzel has employed both hydride sponge (4) and proton sponge (5, Scheme 10) as a frustrated Lewis pair (FLP) system to activate a range of small molecules, including PH 3 . 59 5 undertakes proton abstraction while 4 forms the phosphide adduct, and the authors note that QTAIM (quantum theory of atoms in molecules) analysis indicated that the B−P bond interaction is the most covalent B−E bond interaction when compared to the N, As, O, S, and Se analogues in the study. Interestingly, when the hydride sponge is modified, although PH 3 undergoes the same activation event, AsH 3 undergoes a further transformation with the MeCN solvent. If we consider the wealth of transformations that can be undertaken both stoichiometrically and catalytically using FLPs, 60−63 in particular reactions that use H 2 that has been activated, 64,65 this hints that this could be a rich vein of research. Indeed, modification of the FLP structure could enable enantioselective transfer of the H 2 P − and H + fragments to an organic substrate.

FUTURE TARGETS
At this stage it is useful to consider several aspects as we look toward future synthetic development targets with PH 3 or MPH 2 . In an atom-economic, chemoselective manner, with wide-ranging functional group tolerance, key targets should include the following: 1. Controlled synthesis of primary or secondary or tertiary organophosphines. Reactions need to avoid the formation of mixtures that require complicated cleanup procedures or additional reduction steps to access the P(III) species from the P(V) phosphine oxide; 2. The synthesis of unsymmetrically substituted phosphines from PH 3 or MPH 2 and ultimately C-or Pstereogenic phosphines; 3. The preparation of P−Ar phosphines from PH 3 or MPH 2 , e.g. PAr 3 through to P*Ar 1 Ar 2 Ar 3 selectively; 4. Unique methods not only to activate PH 3 but also undertake onward functionalization, e.g. chemistry beyond hydrofunctionalization. However, to make such advances PH 3 and MPH 2 needs to become more accessible to a wider range of researchers. Indeed, we envisage that many advances will be possible simply through PH 3 (or analogues of PH 3 ) being used more widely in research.

ALTERNATIVE SOURCES OF PH 3
The industrial standard for the production of PH 3 is the basemediated disproportionation of white phosphorus, in the socalled Hoesch process. 66 P 4 is treated with sodium or potassium hydroxide at slightly elevated temperatures (50°C ). With very careful conditions the gas can be collected in ∼95% purity, though this procedure is not particularly practical for a research laboratory. The lab-scale synthesis of PH 3 has been achieved in a number of ways: by the treatment of PCl 3 with Na metal (followed by hydrolysis), 67 the high-temperature treatment of black phosphorus in liquid hydrogen, 68 and the pyrolysis of either hypophosphorous acid, phosphorous acid, or a salt of one of these acids. 69 In 1967, the pyrolysis of phosphorous acid was described as the "most convenient" method for the generation of PH 3 ; 69 however, in a modern Handling pressurized gases, irrespective of toxicity, requires a level of rigor that is not necessarily required when handling solids. Recent reports on the use of metal phosphides, e.g. Zn 3 P 2 , AlP, and Mg 3 P 2 , for the in situ release of PH 3 by digestion using an acid, e.g. HCl, provide a route to PH 3 research that was previously inaccessible to many. However, PH 3 is still released from the metal phosphide; indeed these phosphides are routinely used as pesticides because of their ability to release PH 3 on ingestion, which is fatal. Therefore, although easy to obtain, inexpensive (approximately $74 per kg 72 ), and easy to handle, the same level of care and safety assessment should be taken when handling these simple salts as handling PH 3 gas cylinders.
One of the earliest reports on the in situ generation of PH 3 from a metal phosphide (Zn 3 P 2 ) for the preparation of highvalue P−C bonds was reported by Dorfman and Levina in 1992. 73 The authors employ stoichiometric CuCl 2 or Cu-(OAc) 2 , which, in the presence of pyridine in the coordination sphere, is proposed to acidify the P−H bond in PH 3 , forming a putative Cu-phosphide intermediate along with HCl/HOAc. It is postulated that the resonance structure of pyridine is such that it renders the ortho-and para-positions δ+, and this, coupled with the proximity of the ortho-position to the copper center, renders this position prone to attack by H 2 P − , generating the tris(pyridin-2-yl)phosphane product selectively (Scheme 11). PH 3 generated by decomposition of Zn 3 P 2 has been detailed more recently by Ball 74 and Wolf. 75 Ball has elegantly demonstrated the application of in situ generated PH 3 for the synthesis of tert-alkyl phosphonium triflates, where the byproduct of the reaction is TMSOAc. Due to the high levels of substitution these products cannot be formed using a hydrophosphination route, while the conventional route to secondary alkyl phosphines, R 2 PH, would employ PCl 3 and organomagnesium or organolithium reagent, followed by reduction of the remaining P−Cl bond with a hydride reagent. Ball has shown that these phosphonium salts can then be converted into the secondary phosphine chloride on reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and CCl 4 , transformed into their BH 3 protected phosphine congener (using DBU/BH 3 ·SMe 2 ), benzylated (BnBr then protected using BH 3 ·SMe 2 ) or oxidized to the phosphine oxide (using K 2 CO 3 then H 2 O 2 ), Scheme 12.
Using a similar reaction setup to Ball, where Zn 3 P 2 is digested using HCl in an H-tube and the in situ generated PH 3 can then react with substrate in the second chamber, Wolf employed iridium photocatalyst (6) NEt 3 , PhI, and blue LEDs to prepare Ph 4 P + I − in a 35% yield after 48 h (Scheme 13).
However, use of NaPH 2 as an alternative to PH 3 was more successful, generating the product in 77% yield after 24 h. Extending the substrate scope beyond PhI, but continuing to use NaPH 2 , the authors show selective triarylation using sterically encumbered 2-methyliodobenzene (63% Ar 3 P with no other arylation products observed) and 2-methoxyiodobenzene (42% Ar 4 P + observed only). While 4-methyliodobenzene gives 64% Ar 4 P + /<5% Ar 3 P, 3-methyliodobenzene gives 61%/6% as Ar 4 P + /Ar 3 P and 3-methoxyiodobenzene gives 53%/<5% as Ar 4 P + /Ar 3 P. The remaining ArI substrates give less attractive ratios of Ar 4 P + /Ar 3 P and/or conversions below 50%. A change to an organophotocatalyst (7) can lead to modest adjustments in the ratio/conversion to product(s). The reaction mechanism is postulated to proceed via sequential Reaction profiling shows a rapid buildup of Ph 2 PH as a major species, along with PhPH 2 , which after 5 h are depleted as the onward reaction of these intermediates takes place, with Ar 4 P + eventually being the dominant product. The reaction requires 2 mol % 6, 11 equiv of ArI, and 15 equiv of NEt 3 (or 10 mol % 7, 13 equiv of ArI, 16 equiv of NEt 3 ); clearly elegant but, excitingly, with room for modification and diversification. 6.2. In Situ PH 3 Generation from P(OR) 3 . Liptrot and coworkers recently presented a Cu-catalyzed route to generate PH 3 in 30 min from P(OPh) 3 , using HBpin as a reducing agent. PH 3 was generated in 89% conversion on a 0.1 mmol scale. The in situ generated PH 3 was then directly implemented in the quantitative catalytic hydrophosphination of phenyl isocyanate in a two-pot procedure. 76

Reactions of MPH 2 with p-Block Compounds.
Alkali metal sources of H 2 P − , e.g. LiPH 2 , NaPH 2 , KPH 2 , have been largely ignored in the literature until very recently, but given that they are prepared from PH 3 and clearly have the potential to act as an alternative source of PH 3 (c.f., Wolf), they are an intriguing reagent that deserves further investigation. Their limited use until now may be linked to the routes of synthesis and the instability of these MPH 2 species. Joannis reported the first synthesis of Na and K dihydrogenphosphide in 1894; 77,78 these compounds were further studied alongside the synthesis of LiPH 2 . 79−84 Later still, the rubidium 85 and cesium analogues were reported and the series of alkali metal dihydrogenphosphides were further characterized. 86 These species were prepared by condensing PH 3 in NH 3 (l) and reacting with the metal or metal amide. Handling the Li and Na adduct is not trivial; LiPH 2 decomposes at room temperature while NaPH 2 is noted to decompose above 393 K. The KPH 2 and RbPH 2 species are noted to decompose above 476 K, making them a robust reagent, and it is thus surprising that KPH 2 has not been used more widely in the literature. The poor solubility of KPH 2 can be improved by the addition of 18-crown-6 (catalytic quantities can be used) and/ or the preparation of phthalimide anion adducts. 87 It is worth noting that other routes to H 2 P − anion adducts (e.g., phthalate, alkoxide complexes) are known. 88,89 Several rudimentary transformations of MPH 2 have been reported, where the products are often species that we could envisage as being useful building blocks ready for further reaction or functionalization. For example, Hanssgen reported the preparation of the planar 4-membered heterocycle [(tBu 2 SnPH) 2 ] from tBu 2 SnCl 2 and NaPH 2 (Scheme 14a). 90 Driess has used a dehydrocoupling-type reaction to prepare a dihydrophosphido-aluminium compound [(iBu 2 AlPH 2 ) 3 ] which also operates as an effective H 2 P − transfer agent, forming tris(phosphane) or tetrakis(phosphaneyl)silane/germane products from the trichlorosilane or tetrachlorosilane/ germane precursor (Scheme 14b). 91 Scheer has undertaken salt metathesis reactions of NaPH 2 with IPrGaHCl 2 (8) and the Al analogue (8′) to generate the corresponding bis-(dihydrophosphide) complexes (9/9′, Scheme 14c). 92 Hassler undertook a study into hypersilyl substituted phosphanes and, as part of this investigation, employed PH 3 or NaPH 2 to prepare tris(trimethylsilyl)silyldihydrophosphide (10). This species can undergo deprotonation with KOtBu, forming (Me 3 Si) 3 SiPHK (11), which is remarkably stable at room temperature, and can undergo reductive coupling to generate a mixture of the meso-and rac-isomers (12, Scheme 14d). This reductive coupling step involves reaction with tBu 2 Hg or 1,2dibromoethane; the latter indicates that the phosphide is not particularly nucleophilic in that a P−C bond is not formed between (Me 3 Si) 3 SiPHK and Br 2 (CH 2 ) 2 . 93 Again, this latter point is intriguing and could be further investigated.
In 1982 Issleib reported on the use of KPH 2 to form [3.3.1]bicycle 14 by reaction with diallyl(chloromethyl)(methyl)silane (13) (Scheme 15a), and this type of protocol has since been used to access other phosphabicycles. 94,95 A similar approach was taken to prepare a mixture of the cis-and trans-[4.4.0]-bicycle (15, Scheme 15b). These compounds were also complexed to Ni(CO) 4 , and the resulting L cis Ni(CO) 3 and L trans Ni(CO) 3 have similar Tolman Electronic Parameters (2063 and 2062 cm −1 respectively), which are very close to the σ-donor-only properties of PMe 3 (2064 cm −1 ). 96 Both reports indicate that interesting, unique phosphorus architectures can be prepared in a controlled way using PH 3 derivatives.
Baulder employed KPH 2 in the degradation of red phosphorus to access the P 5 anion, pentaphosphacyclopentadienide (the all-P analogue of the cyclopentadienyl anion) (16, Scheme 16a). With purification only requiring filtration and removal of PH 3 gas, this offers an attractive alternative to the fractional crystallization previously reported for the synthesis from P 4 . 97 Further to this example, use of NaPH 2 (or Lewis base adduct analogues) is mostly limited to main group bond transformations. For example, Gruẗzmacher reacted [Na 5 (OtBu) 4 PH 2 ] with 1,2-bis(chloro(phenyl)methylene)hydrazine to prepare a 1,2,4-diazaphospholide (17, Scheme 16b); 89 the group also prepared the heavy isocyanate Na(OCP), sodium phosphaethynolate, from reaction of NaPH 2 with CO (Scheme 16c). 98 The onward reactivity of Na(OCP) (and Lewis base/solvent adducts) has been studied by Gruztmacher in terms of probing nucleophility in the presence of group 14 compounds, 99 while Stephan has employed Guẗztmacher's germanium compound, Ph 3 GePCO, to prepare the phosphorus-containing analogue of N,Ndimethylformamide (18), which can undergo coordination chemistry with ruthenium forming 19 (Scheme 16d). 100

Reactions of MPH 2 with Carbonyl-Containing
Compounds. An early report on potential applications in organic synthesis was provided by Liotta. 101 Reaction of aryl or alkyl benzoates with KPH 2 in the presence of a catalytic amount of 18-crown-6 (10 mol %) generates potassium benzoyl phosphide (20, Scheme 17). This can undergo protonation with acid (trifluoroacetic acid, TFA) or methylation with MeI, but in both cases the products are unstable and decompose to generate dibenzoylphosphines (21). As we might expect, based simply on atomic size, the authors note no partial double character due to P atom lone pair/carbonyl πorbital overlap (as we normally see with amides); if decomposition pathways can be controlled it may be possible to develop useful chemistry that diverges from that of amides.
Goicoechea has reported the synthesis of Na(OCP) from the reaction of NaPH 2 with isocyanate Dipp-NCO (though notably the syntheses of Na(OCP) have been reported from NaPH 2 directly and PH 3 as a feedstock). 102 Na(OCP) goes on to react with isocyanates, generating structurally interesting main group compounds such as 22 (Scheme 18a). 103 Interestingly, use of the potassium analogue, [K(18-crown-6)(OCP)], gives a different product distribution compared to that obtained using Na(OCP) (Scheme 18b), while the products obtained using Na(OCP) vary based on the substituents on the isocyanate (compare Scheme 18a and 18b, bottom), 104 hinting at the diversity of synthesis that could be achieved if these reagents were more widely studied.
Analogous to the work of Liotta on esters, 101 reaction of NaPH 2 with CO 2 gives a phosphine carboxylate, which can then undergo onward reaction with silyl chlorides to form phosphine carboxylate silylesters (Scheme 19). 105 Goicoechea has also shown that NaPH 2 can react with dimethyl cyanocarbonimidate in one step to form the heteroallene anion species 23, or in a stepwise fashion via the (carboximidate)phosphide 24 (Scheme 20). 24 can undergo reaction with Ph 3 GeCl to form a dimeric species product. 106 Many of the reactions discussed thus far are rooted in fundamental research, and therefore for many of the reactions that could be termed transformations of main group species, it may be difficult to envisage the relevance of these compounds to the organophosphorus, organic chemistry or applied chemistry communities. While these main group compounds are often challenging to prepare and handle, organic transformations of carboxylic acids and allenes are well-known: we have yet to discover if the aforementioned phosphoruscontaining species undergo the same transformations, e.g. allenes undergoing a rich array of addition and cyclization reactions. 107 Gudat prepared a series of diazaboroles, including the PH 2 species (26) from KPH 2 and the bromodiazaborole precursor (25, Scheme 21a). The computational component of this study notes the covalent nature of the P−B σ-bond, along with the potential for these main group compounds to act as P-donor ligands. 108 This ligand system has been incorporated into a scandium β-diketiminate complex, 109

Scheme 21. (a) Gudat and Co-workers Prepared and
Studied the Electronic Properties of Phosphino-Diazaboroles, While (b) Chen, Maron and Co-workers Employed the System in Coordination Chemistry a already reported using a bulky 2,4,6-tBu-phenyl phosphinidene Zr 110 or Th 111 complex, which operate in a stoichiometric fashion (akin to that possible with Tebbe's reagent 112 ).

Reactions of MPH 2 with Compounds of the dand f-Block.
Using a triamidoamine ligand, but one that is less bulky than that used to activate N 2 , 113 Schrock was able to demonstrate the reactivity of a homologous series of Mo and W amido, phosphide, and arsenido complexes, employing LiPH 2 or LiEPhH (E = P, As) or trimethylsilylazide (TMSN 3 ) to install the M�E bond (Scheme 22a). 114 Their onward reaction with MeOTf to form the imido, phosphinidene, and arsinidene complexes (27) was studied, and the authors note that the Mo-phosphinidine complex decomposes in solution at room temperature whereas the W analogue does not. Similarly, the Mo arsinidine triflate was very unstable and could not undergo elemental analysis. The amido complex undergoes reduction in the presence of LiC 8 H 8 to generate the Mo(V) product (28, Scheme 22b). This chemistry is important, because of not only the analogies we can draw between phosphorus and carbon but also the wealth of chemistry undertaken on the activation and functionalization of metal nitrido complexes, in particular their conversion to amines. 115−118 If we consider the importance of metal−carbon double bonds in catalysis, e.g. in catalytic metathesis reactions, and the allegory between P and C, then it is vital that fundamental studies into bonding and reactivity of metal−P multiply bonded species are undertaken. In this regard, NaPH 2 has been used by Liddle to generate uranium and thorium phosphanide (29/31) and phosphinidene (30/32) complexes (Scheme 23a and 23b). 119,120 Liddle also presented a follow-up paper on the analogous Zr complex (33), which reacts in a similar way to the uranium and thorium analogues (forming the respective phosphanide and phosphinidene compounds, 34 and 35, Scheme 23c). 121 We can draw links to possible onward organic Scheme 22. Schrock and Co-workers Have Undertaken a Systematic Study on the Coordination Chemistry of Molybdenum and Tungsten Amides, Phosphides, and Arsenides Scheme 23. (a, b) Liddle's Studies on the Phosphanide and Phosphinidene Chemistry of the Actinides; a (c) Studies on the Analogous Zr Complex a Na(12c4) 2 cations omitted for clarity, and 12-crown-4 (12c4) and benzo-15-crown-5 abbreviated for clarity (b15c5).
Journal of the American Chemical Society pubs.acs.org/JACS Perspective transformations by looking at the insertion chemistry reported by Stephan,110 Walter, 111 and Walensky, where benzophenone was shown to insert into the Th−P bond of a bulkier mesityl analogue, 122 and from the work of Mindiola on Tiphosphinidene complexes and their hydrophosphination reactivity, although these species do require kinetic stabilization by use of a bulky organophosphine reagent. 123 Driess has further elaborated the silylene chemistry of PH 3 58 by taking a nickel-silylene species and demonstrating the coordination chemistry of PH 2 (derived from Li(dme)PH 2 or Li(tmeda)PH 2 ), generating 36 (Scheme 24) and subsequent isomerization chemistry of the η 2 -species to generate 37/38. 124 Finally, Scheer has also employed NaPH 2 to generate a Mo dimer with a mixed P/As bridge (39, Scheme 25). 125 A fundamental study, but one where we can envisage links to higher order main group polymer chains 126 with unique properties.

CONCLUSIONS AND OUTLOOK
The utilization of PH 3 in synthesis is undoubtedly an untapped well, and this is understandable owing to the significant challenges in manipulating pressurized cylinders of such a hazardous gas. However, the recent reports of in situ PH 3 generation offer a much safer alternative to its traditional manipulation. These new operationally simple methods have the potential to revolutionize phosphorus research (which is itself prevalent across a wide range of disciplines). More readily accessible PH 3 sources will also provide easier access to MPH 2 species (where M is an alkali metal), which are already experiencing a renaissance and are proving vital to access novel phosphorus-containing species (vide supra).
Considerable efforts have gone into the functionalization of P 4 and PCl 3 , and adding PH 3 to the list of readily accessible phosphorus starting materials will grant access to a rich vein of research. The prospect of catalytically activating PH 3 to access useful phosphorus reagents is exciting, and with reports of M�PH and M−PH 2 species, this endeavor feels more attainable than ever. The question remains: how to take M�PH, M−PH 2 and undertake transformations of these species that go beyond hydrophosphination chemistry reported in the 1980s and 1990s?

Funding
Funding awarded by the EPSRC (SL, RLW) and The Leverhulme Trust (TMH, RLW).